Transglutaminase Activity as a Possible Molecular Mechanism in the Etiopathogenesis of Neurodegenerative Diseases

Abstract

characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review focuses on the possible molecular mechanisms responsible for such diseases and on the possible therapeutic effects of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity. BIOCHEMISTRY OF THE TRANSGLUTAMINASESTransglutaminases (TGs, E.C. 2.3.2.13) are family of Ca 2+ -dependent enzymes which catalyze post-translational modifications of proteins. Examples of TG-catalyzed reactions include: (1) acyl transfer between the g-carboxamide group of a protein/polypeptide glutaminyl residue and the e-amino group of a protein/polypeptide lysyl residue; (2) attachment of a polyamine to the g-carboxamide of a glutaminyl residue; (3) deamidation of the g-carboxamide group of a protein/polypeptide glutaminyl residue (Figure 1) [1,2] . The reactions catalyzed by TGs occur by a two-step mechanism (ping-pong type), (Figure 2 ABSTRACTTransglutaminases are a family of Ca 2+ -dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono-or bi-substituted/crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological and pathological processes. In particular, transglutaminase activity has been shown to be

Microbial Transglutaminase Is a Very Frequently Used Food Additive and Is a Potential Inducer of Autoimmune/Neurodegenerative Diseases

“…Since leaky gut/brain are associated, those factors might impact brain activity and be involved in neurodegenerative diseases and neurological/psychiatric presentations in ADs, including CD [72,73]. Indeed, processed food additives, crossreactive nutrients, alpha enolase, tTG and potentially mTG are suspected to drive various human chronic disease, ADs and neurodegenerative included [9,14,[74][75][76]. However, some questions deserve more studies.…”